tbuckley/cabot-search huggingface dataset:
Emphasizing Study Selection in a Review of Statin Treatment Effects and Low-Density Lipoprotein Cholesterol—Reply
Authors: Paula Byrne, Robert DuBroff
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Recovery from the damage of cranial radiation modulated by memantine, an NMDA receptor antagonist, combined with hyperbaric oxygen therapy
Authors: Yohei Hokama, Masahiko Nishimura, Ryoichi Usugi, Kyoko Fujiwara, Chiaki Katagiri, Hiroshi Takagi, Shogo Ishiuchi
Journal: Neuro-Oncology (2022)

Abstract Background Radiotherapy is an important treatment option for central nervous system malignancies. However, cranial radiation induces hippocampal dysfunction and white matter injury; this leads to cognitive dysfunction, and results in a reduced quality of life in patients. Excitatory glutamate signaling through N-methyl-d-aspartate receptors (NMDARs) plays a central role both in hippocampal neurogenesis and in the myelination of oligodendrocytes in the cerebrum. Methods We provide a method for quantifying neurogenesis in human subjects in live brain during cancer therapy. Neuroimaging using originally created behavioral tasks was employed to examine human hippocampal memory pathway in patients with brain disorders. Results Treatment with memantine, a non-competitive NMDAR antagonist, reversed impairment in hippocampal pattern separation networks as detected by functional magnetic resonance imaging. Hyperbaric preconditioning of the patients just before radiotherapy with memantine mostly reversed white matter injury as detected by whole brain analysis with Tract-Based Spatial Statics. Neuromodulation combined with the administration of hyperbaric oxygen therapy and memantine during radiotherapy facilitated the restoration of hippocampal function and white matter integrity, and improved higher cognitive function in patients receiving cranial radiation. Conclusions The method described herein, for diagnosis of hippocampal dysfunction, and therapeutic intervention can be utilized to restore some of the cognitive decline experienced by patients who have received cranial radiation. The underlying mechanism of restoration is the production of new neurons, which enhances functionality in pattern separation networks in the hippocampi, resulting in an increase in cognitive score, and restoration of microstructural integrity of white matter tracts revealed by Tract-Based Spatial Statics Analysis.
Novel Smooth Muscle Ca <sup>2+</sup> -Signaling Nanodomains in Blood Pressure Regulation
Authors: Yen-Lin Chen, Zdravka Daneva, Maniselvan Kuppusamy, Matteo Ottolini, Thomas M. Baker, Eliska Klimentova, Soham A. Shah, Jennifer D. Sokolowski, Min S. Park, Swapnil K. Sonkusare
Journal: Circulation (2022)

Ca2+ signals in smooth muscle cells (SMCs) contribute to vascular resistance and control blood pressure. Increased vascular resistance in hypertension has been attributed to impaired SMC Ca2+ signaling mechanisms. In this regard, transient receptor potential vanilloid 4 (TRPV4SMC) ion channels are a crucial Ca2+ entry pathway in SMCs. However, their role in blood pressure regulation has not been identified.We used SMC-specific TRPV4-/- (TRPV4SMC-/-) mice to assess the role of TRPV4SMC channels in blood pressure regulation. We determined the contribution of TRPV4SMC channels to the constrictor effect of α1 adrenergic receptor (α1AR) stimulation and elevated intraluminal pressure: 2 main physiologic stimuli that constrict resistance-sized arteries. The contribution of spatially separated TRPV4SMC channel subpopulations to elevated blood pressure in hypertension was evaluated in angiotensin II-infused mice and patients with hypertension.We provide first evidence that TRPV4SMC channel activity elevates resting blood pressure in normal mice. α1AR stimulation activated TRPV4SMC channels through PKCα (protein kinase Cα) signaling, which contributed significantly to vasoconstriction and blood pressure elevation. Intraluminal pressure-induced TRPV4SMC channel activity opposed vasoconstriction through activation of Ca2+-sensitive K+ (BK) channels, indicating functionally opposite pools of TRPV4SMC channels. Superresolution imaging of SMCs revealed spatially separated α1AR:TRPV4 and TRPV4:BK nanodomains in SMCs. These data suggest that spatially separated α1AR-TRPV4SMC and intraluminal pressure-TRPV4SMC-BK channel signaling have opposite effects on blood pressure, with α1AR-TRPV4SMC signaling dominating under resting conditions. Furthermore, in patients with hypertension and a mouse model of hypertension, constrictor α1AR-PKCα-TRPV4 signaling was upregulated, whereas dilator pressure-TRPV4-BK channel signaling was disrupted, thereby increasing vasoconstriction and elevating blood pressure.Our data identify novel smooth muscle Ca2+-signaling nanodomains that regulate blood pressure and demonstrate their impairment in hypertension.
Prevalence and Vascular Distribution of Multiterritorial Atherosclerosis Among Community-Dwelling Adults in Southeast China
Authors: Yuesong Pan, Jing Jing, Xueli Cai, Zening Jin, Suying Wang, Yilong Wang, Chunlai Zeng, Xia Meng, Jiansong Ji, Long Li, Lingchun Lyu, Zhe Zhang, Lerong Mei, Hao Li, Shan Li, Tiemin Wei, Yongjun Wang
Journal: JAMA Network Open (2022)

Data are limited on the prevalence and vascular distribution of multiterritorial atherosclerotic plaque and stenosis in community populations.To investigate the prevalence and vascular distribution of multiterritorial atherosclerotic plaque and stenosis in older, community-dwelling populations in China.This cross-sectional study was based on the baseline survey from the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study, a population-based prospective cohort study that enrolled community-dwelling adults aged 50 to 75 years based on cluster sampling from 6 villages and 4 living communities of Lishui city in southeast China. Data were collected from May 2017 to September 2019 and analyzed from September to November 2021.Atherosclerotic plaque and stenosis at baseline were assessed in multiple vascular territories. Brain vessel wall magnetic resonance imaging (MRI) for intracranial and extracranial arteries; computed tomography angiography (CTA) for coronary, subclavian, aorta, renal, and iliofemoral arteries; and ankle-brachial index for peripheral arteries were performed at baseline survey. The extent of atherosclerosis was assessed according to the number of these 8 vascular sites affected, and polyvascular lesions were defined as at least 2 affected sites.A total of 3433 of 4202 invited individuals consented to participate in the study. After excluding 366 participants with contraindications for MRI or CTA scanning, with life expectancies of 4 years of fewer, or with mental disease, a total of 3067 community-dwelling adults were enrolled. The mean (SD) age was 61.2 (6.7) years; 1640 (53.5%) were women, and 74 (2.4%) had prevalent ASCVD. Most participants (2870 [93.6%]) had atherosclerotic plaques in at least 1 vascular territory. Atherosclerotic plaques were mostly detected in the aorta (2419 [79.6%]) and iliofemoral arteries (2312 [75.8%]), followed by subclavian (1500 [49.8%]), coronary (1366 [44.9%]), extracranial (1110 [36.4%]), renal (873 [28.7%]), and intracranial (542 [17.7%]) arteries. A substantial proportion of participants (1180 [38.5%]) had arterial stenosis of 50% or greater, predominantly affecting the coronary (542 [17.8%]) and iliofemoral (527 [17.3%]) arteries. Polyvascular atherosclerotic plaque was observed in 2541 participants (82.8%), with 1436 (46.8%) with plaque affecting 4 or more vascular territories, and polyvascular stenosis was observed in 412 patients (13.4%).In this study, atherosclerotic plaque was highly prevalent in the older community population in China, and a substantial proportion of individuals reach stenosis of 50% or greater.
Gabapentin Increasingly Implicated in Overdose Deaths
Authors: Bridget M. Kuehn
Journal: JAMA (2022)

Postmortem toxicology tests detected gabapentin in almost 1 in 10 US overdose deaths between 2019 and 2020. In about half of the cases, a medical examiner or coroner ruled the drug was a cause of the death, according to a report from the CDC’s Division of Overdose Prevention.
Covid-19: Pausing immune suppressing drugs enhances antibody response to boosters, study shows
Authors: Jacqui Wise
Journal: BMJ (2022)

Covid-19: Pausing immune suppressing drugs enhances antibody response to boosters, study shows Jacqui WiseInterrupting methotrexate treatment for two weeks after a covid-19 vaccine booster doubles the antibody responses of immune suppressed people, new research 1 has shown.The improvement in antibody response was maintained for three months, the research published in Lancet Respiratory Medicine found.And although the temporary suspension of immune suppressant treatment increases the risk of disease flare ups, most patients could self-manage these.Methotrexate is the most commonly used immune suppressing drug, with around 1.3 million people in the UK prescribed it for inflammatory conditions such as rheumatoid arthritis and skin conditions such as psoriasis.Until now there has been conflicting advice on whether to continue or interrupt methotrexate treatment after covid-19 vaccination.
Extracellular vesicles: Emerging frontiers in wound healing
Authors: Mangesh D. Hade, Caitlin N. Suire, James Mossell, Zucai Suo
Journal: Medicinal Research Reviews (2022)

Abstract Extracellular vesicles are membranous particles, ranging from 30 nm to 10 µm in diameter, which are released by nearly all cell types to aid in intercellular communication. These complex vesicles carry a multitude of signaling moieties from their cell of origin, such as proteins, lipids, cell surface receptors, enzymes, cytokines, metabolites, and nucleic acids. A growing body of evidence suggests that in addition to delivering cargos into target cells to facilitate intercellular communication, extracellular vesicles may also play roles in such processes as cell differentiation and proliferation, angiogenesis, stress response, and immune signaling. As these vesicles have natural biocompatibility, stability in circulation, low toxicity, and low immunogenicity, and serve as efficient carriers of molecular cargos, these nanoparticles are ideal therapeutic candidates for regenerative medicine. Exploring and identifying the homeostatic functions of extracellular vesicles may facilitate the development of new regenerative therapies. In this review, we summarize the wound healing process, difficulties in stem cell therapies for regenerative medicine, and the applications of mesenchymal stromal cell‐derived extracellular vesicles in improving and accelerating the wound healing process.
Emerging role of exosomes in cancer progression and tumor microenvironment remodeling
Authors: Mahshid Deldar Abad Paskeh, Maliheh Entezari, Sepideh Mirzaei, Amirhossein Zabolian, Hossein Saleki, Mohamad Javad Naghdi, Sina Sabet, Mohammad Amin Khoshbakht, Mehrdad Hashemi, Kiavash Hushmandi, Gautam Sethi, Ali Zarrabi, Alan Prem Kumar, Shing Cheng Tan, Marios Papadakis, Athanasios Alexiou, Md Asiful Islam, Ebrahim Mostafavi, Milad Ashrafizadeh
Journal: Journal of Hematology & Oncology (2022)

Abstract Cancer is one of the leading causes of death worldwide, and the factors responsible for its progression need to be elucidated. Exosomes are structures with an average size of 100 nm that can transport proteins, lipids, and nucleic acids. This review focuses on the role of exosomes in cancer progression and therapy. We discuss how exosomes are able to modulate components of the tumor microenvironment and influence proliferation and migration rates of cancer cells. We also highlight that, depending on their cargo, exosomes can suppress or promote tumor cell progression and can enhance or reduce cancer cell response to radio- and chemo-therapies. In addition, we describe how exosomes can trigger chronic inflammation and lead to immune evasion and tumor progression by focusing on their ability to transfer non-coding RNAs between cells and modulate other molecular signaling pathways such as PTEN and PI3K/Akt in cancer. Subsequently, we discuss the use of exosomes as carriers of anti-tumor agents and genetic tools to control cancer progression. We then discuss the role of tumor-derived exosomes in carcinogenesis. Finally, we devote a section to the study of exosomes as diagnostic and prognostic tools in clinical courses that is important for the treatment of cancer patients. This review provides a comprehensive understanding of the role of exosomes in cancer therapy, focusing on their therapeutic value in cancer progression and remodeling of the tumor microenvironment. Graphical Abstract
Streamlining breast cancer and colorectal cancer biosimilar regulations to improve treatment access in Latin America: an expert panel perspective
Authors: Enrique Teran, Henry Gomez, Damian Hannois, Mauricio Lema, William Mantilla, Mariana Rico-Restrepo, Elizabeth McElwee, Noe Castro Sanchez, Natalia Valdivieso, Manuel Antonio Espinoza
Journal: The Lancet Oncology (2022)
Maternal Fc-mediated non-neutralizing antibody responses correlate with protection against congenital human cytomegalovirus infection
Authors: Eleanor C. Semmes, Itzayana G. Miller, Courtney E. Wimberly, Caroline T. Phan, Jennifer A. Jenks, Melissa J. Harnois, Stella J. Berendam, Helen Webster, Jillian H. Hurst, Joanne Kurtzberg, Genevieve G. Fouda, Kyle M. Walsh, Sallie R. Permar
Journal: Journal of Clinical Investigation (2022)

Human cytomegalovirus (HCMV) is the most common congenital infection and a leading cause of stillbirth, neurodevelopmental impairment, and pediatric hearing loss worldwide. Development of a maternal vaccine or therapeutic to prevent congenital HCMV has been hindered by limited knowledge of the immune responses that protect against HCMV transmission in utero. To identify protective antibody responses, we measured HCMV-specific IgG binding and antiviral functions in paired maternal and cord blood sera from HCMV-seropositive transmitting (n = 41) and non-transmitting (n = 40) mother-infant dyads identified via a large, US-based, public cord blood bank. We found that high-avidity IgG binding to HCMV and antibody-dependent cellular phagocytosis (ADCP) were associated with reduced risk of congenital HCMV infection. We also determined that HCMV-specific IgG activation of FcγRI and FcγRII was enhanced in non-transmitting dyads and that increased ADCP responses were mediated through both FcγRI and FcγRIIA expressed on human monocytes. These findings suggest that engagement of FcγRI/FcγRIIA and Fc effector functions including ADCP may protect against congenital HCMV infection. Taken together, these data can guide future prospective studies on immune correlates against congenital HCMV transmission and inform HCMV vaccine and immunotherapeutic development.
Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence
Authors: Simon Linder, Marlous Hoogstraat, Suzan Stelloo, Nils Eickhoff, Karianne Schuurman, Hilda de Barros, Maartje Alkemade, Elise M. Bekers, Tesa M. Severson, Joyce Sanders, Chia-Chi Flora Huang, Tunc Morova, Umut Berkay Altintas, Liesbeth Hoekman, Yongsoo Kim, Sylvan C. Baca, Martin Sjöström, Anniek Zaalberg, Dorine C. Hintzen, Jeroen de Jong, Roelof J.C. Kluin, Iris de Rink, Claudia Giambartolomei, Ji-Heui Seo, Bogdan Pasaniuc, Maarten Altelaar, René H. Medema, Felix Y. Feng, Amina Zoubeidi, Matthew L. Freedman, Lodewyk F.A. Wessels, Lisa M. Butler, Nathan A. Lack, Henk van der Poel, Andries M. Bergman, Wilbert Zwart
Journal: Cancer Discovery (2022)

In prostate cancer, androgen receptor (AR)-targeting agents are very effective in various disease stages. However, therapy resistance inevitably occurs, and little is known about how tumor cells adapt to bypass AR suppression. Here, we performed integrative multiomics analyses on tissues isolated before and after 3 months of AR-targeting enzalutamide monotherapy from patients with high-risk prostate cancer enrolled in a neoadjuvant clinical trial. Transcriptomic analyses demonstrated that AR inhibition drove tumors toward a neuroendocrine-like disease state. Additionally, epigenomic profiling revealed massive enzalutamide-induced reprogramming of pioneer factor FOXA1 from inactive chromatin sites toward active cis-regulatory elements that dictate prosurvival signals. Notably, treatment-induced FOXA1 sites were enriched for the circadian clock component ARNTL. Posttreatment ARNTL levels were associated with patients' clinical outcomes, and ARNTL knockout strongly decreased prostate cancer cell growth. Our data highlight a remarkable cistromic plasticity of FOXA1 following AR-targeted therapy and revealed an acquired dependency on the circadian regulator ARNTL, a novel candidate therapeutic target.Understanding how prostate cancers adapt to AR-targeted interventions is critical for identifying novel drug targets to improve the clinical management of treatment-resistant disease. Our study revealed an enzalutamide-induced epigenomic plasticity toward prosurvival signaling and uncovered the circadian regulator ARNTL as an acquired vulnerability after AR inhibition, presenting a novel lead for therapeutic development. See related commentary by Zhang et al., p. 2017. This article is highlighted in the In This Issue feature, p. 2007.
Abstract Book for the 27th Congress of the European Hematology Association
Journal: HemaSphere (2022)

Log in or Register Get new issue alertsGet alerts Submit your manuscript Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. Subscribe to eTOC Secondary Logo Journal Logo All Articles Images Videos Podcasts Blogs Advanced Search Toggle navigation Register Login Articles & Issues Latest ArticlesCurrent IssuePrevious Issues Subject Areas Cell and Gene TherapiesHematopoiesisLymphoid MalignanciesMyeloid MalignanciesRed Cell and Iron MetabolismThrombosis and HemostasisView All Featured Content Latest ArticlesReviews & ControversiesGuidelinesHemaTopicsHemaBitesEHA Research RoadmapCAR T-CellGene TherapyCOVID-19Biosimilars For Authors Instructions for Authors Submit Your PaperBenefits for AuthorsOpen Access Editorial, Legal, and Ethical PoliciesLanguage Editing Services About Us About the JournalEditorial BoardAffiliated SocietyReprintsRights and Permissions All Articles Images Videos Podcasts Blogs Advanced Search
Almost half of people on long term antidepressants can stop without relapsing
Authors: Helen Saul, Deniz Gursul, Samantha Cassidy, Larisa Duffy, Gemma Lewis, Glyn Lewis
Journal: BMJ (2022)

The studyDuffy L, Clarke CS, Lewis G, et al. Antidepressant medication to prevent depression relapse in primary care: the ANTLER RCT. Health Technol Assess 2021;25:69.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/almost-half-people-long-term-antidepressants-stop-without-relapse/.
Common Hand Conditions
Authors: Kelly Bettina Currie, Kashyap Komarraju Tadisina, Susan E. Mackinnon
Journal: JAMA (2022)

Importance Carpal tunnel syndrome, trigger finger, de Quervain tenosynovitis, and basilar (carpometacarpal) joint arthritis of the thumb can be associated with significant disability. Observations Carpal tunnel syndrome is characterized by numbness and tingling in the thumb and the index, middle, and radial ring fingers and by weakness of thumb opposition when severe. It is more common in women and people who are obese, have diabetes, and work in occupations involving use of keyboards, computer mouse, heavy machinery, or vibrating manual tools. The Durkan physical examination maneuver, consisting of firm digital pressure across the carpal tunnel to reproduce symptoms, is 64% sensitive and 83% specific for carpal tunnel syndrome. People with suspected proximal compression or other compressive neuropathies should undergo electrodiagnostic testing, which is approximately more than 80% sensitive and 95% specific for carpal tunnel syndrome. Splinting or steroid injection may temporarily relieve symptoms. Patients who do not respond to conservative therapies may undergo open or endoscopic carpal tunnel release for definitive treatment. Trigger finger, which involves abnormal resistance to smooth flexion and extension (“triggering”) of the affected finger, affects up to 20% of adults with diabetes and approximately 2% of the general population. Steroid injection is the first-line therapy but is less efficacious in people with insulin-dependent diabetes. People with diabetes and those with recurrent symptoms may benefit from early surgical release. de Quervain tenosynovitis, consisting of swelling of the extensor tendons at the wrist, is more common in women than in men. People with frequent mobile phone use are at increased risk. The median age of onset is 40 to 59 years. Steroid injections relieve symptoms in approximately 72% of patients, particularly when combined with immobilization. People with recurrent symptoms may be considered for surgical release of the first dorsal extensor compartment. Thumb carpometacarpal joint arthritis affects approximately 33% of postmenopausal women, according to radiographic evidence of carpometacarpal arthritis. Approximately 20% of patients require treatment for pain and disability. Nonsurgical interventions (immobilization, steroid injection, and pain medication) relieve pain but do not alter disease progression. Surgery may be appropriate for patients unresponsive to conservative treatments. Conclusions and Relevance Carpal tunnel syndrome, trigger finger, de Quervain tenosynovitis, and thumb carpometacarpal joint arthritis can be associated with significant disability. First-line treatment for each condition consists of steroid injection, immobilization, or both. For patients who do not respond to noninvasive therapy or for progressive disease despite conservative therapy, surgical treatment is safe and effective.